Spatio-Temporal Expression Of Channels Nav1.7,Nav1.8 And Cav3.2 In Diabetic Mechanical Allodynia In Rats

Background/Aims:Pain is a debilitating feature reported in patients with peripheral diabetic neuropathy, whose common form is mechanical allodynia(DMA). However, the pathophysiology underlying DMA remains unclear. The purpose of our study was to investigate the spatio-temporal expression of Nav1.7, Nav1.8 and Cav3.2channels in dorsal root ganglia(DRGs) and uncover their roles in the development and maintenance of pain-relatedbehaviors in DMA rat models.Methods:Diabetic models were induced by intraperitoneal injection of a single dose of streptozotocin(STZ, 60 mg/kgbodyweight) in adult male rats, while rats in thecontrol group received citrate buffer only. Toselect the successful DMA model rats, von Frey filaments were used to measurethe paw withdrawal threshold of diabetic model rats in a blindmanner.Blood glucose, body weight and mechanical pain threshold tests were performedbefore STZ or buffer injection to get baseline, and repeated on day3, 7, 14, 21 and 28 after treatment.The methods of western blot and quantitative real-time PCR were employedto measure the expression level of Nav1.7, Nav1.8 and Cav3.2in the L4-6 DRGsof rats.Results:Three days after STZ treatment, the majority of rats developed high levels of blood glucose and their weight increased slowly compared with that of the normal rats. The mechanical pain threshold of diabeticgroup was decreased after modeling day3 to day 21 and persisted until day 28,while the expression level of Nav1.7 proteinwas consistentlyrising over time. Nav1.8 protein level experienced an opposite trend and the changes of Nav1.7, Nav1.8 expression was correlated with the decline of mechanical pain threshold.Western blot and RT-PCR results were parallel and showed that Cav3.2protein and mRNAwere significantly up-regulated at day 7 and day 14 but declined to normal level at day 21 and day 28.Conclusions: In diabetic rats of the same transition period of DMA development we have observed mechanical allodynia is associated with Nav1.7, Nav1.8 and Cav3.2, which might cooperative with each other in different phases. We suggest the following scenario of Nav1.7, Nav1.8 and Cav3.2 modifications during DMA development. At the early stage as the occurrence of DMA, there is a cooperative up-regulation of Nav1.7, Nav1.8 and Cav3.2 expression. However, with Cav3.2 heading back to normal level, the cooperation of up-regulation of Nav1.7 and down-regulation of Nav1.8 leads to the allodynia during the progression period of DMA.